title: Activation of JAK-STAT1 signal transduction pathway in lesional skin and monocytes from patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  To study the activation of Janus protein tyrosine kinase (JAK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway and its inhibitor-signal transducer and activator of transcription-1(SOCS-1) in patients with systemic lupus erythematosus.
  
  
  METHODS
  A total of 45 patients with active systemic lupus erythematosus (SLE) and 30 healthy controls were randomly selected. Western blot was performed to measure the expression of Stat1 protein and phospho-Stat1 protein (an activated form of Stat1 protein) in the monocytes after stimulation with recombinant high mobility group box1 (rHMGB1) at various time points. Expression of Stat1 protein in the skin or lesional skin was also detected. Phasic expressions of SOCS-1 mRNA in the monocytes after rHMGB1 stimulation were detected by real-time reverse transcription-polymerase chain reaction. SOCS-1 gene expression in the skin or lesional skin was also detected.
  
  
  RESULTS
  The expression level of Stat1 proteins in the monocytes from patients with SLE was higher than that from healthy controls (t=9.16, P<0.01) and positively correlated with SLE disease activity index (SLEDAI) (r=0.59, P<0.01). Expression of phospho-Stat1 in the monocytes from SLE patients was time-dependently upregulated after stimulation with rHMGB1 at various time points, while expression of SOCS-1 mRNA remained unchanged (all P>0.05). Expressions of phospho-Stat1 protein and SOCS-1 mRNA in the monocytes from healthy controls were increased transiently after stimulation with rHMGB1 (all P<0.05). Both expressions of phospho-Stat1 protein and SOCS-1 gene in the lesional skin from patients with SLE were upregulated compared with those in normal skin from healthy controls (all P<0.01).
  
  
  CONCLUSIONS
  There are hyperactivation of JAK-STAT1 signaling pathway and negative feedback down-regulation of SOCS-1 in patients with systemic lupus erythematosus. HMGB-1 may be partly involved in the pathogenesis of SLE by the abnormal mediating function of JAK-STAT1 signal transduction pathway.
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.forename: Mei
authors.initials: M
authors.lastname: Yi
authors.forename: Xing
authors.initials: X
authors.lastname: Hu
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Hongfu
authors.initials: H
authors.lastname: Xie
authors.forename: Wu
authors.initials: W
authors.lastname: Zhu
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D024243:HMGB1 Protein / Q000494:pharmacology; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D024243:HMGB1 Protein; D012333:RNA, Messenger; D011994:Recombinant Proteins; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases